The Effects of Dopamine on the Subthreshold Electrophysiological Responses of Rat Prefrontal Cortex Neurons In Vitro

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Abstract
The rat prefrontal cortex is densely innervated by dopaminergic fibres originating in the mesencephalic ventral tegmental area, and dopamine application in vivo has an inhibitory effect. We have studied the effects of dopamine on the persistent sodium current that is present in prefrontal cortex neurons and on the subthreshold electrophysiological responses generated by that current: a slow depolarization and a fast oscillatory activity. Experiments were made in coronal slices of rat frontal cortex (300-400 microns thickness) and intracellular recordings from regularly spiking cells were obtained with 3 M potassium acetate-filled glass microelectrodes (80-150 M omega). Dopamine was applied dissolved in the extracellular medium and, in current-clamp recordings, reversibly inhibited the slow subthreshold depolarization. Dopamine was ineffective when applied after tetrodotoxin (1 microM) had blocked the action potentials. This inhibition was dose-dependent in the range of 0.1-10 microM). Dopamine, applied at 10 microM, decreased the steady-state firing frequency and also inhibited the subthreshold fast oscillatory activity. The currents activated in the subthreshold range were recorded with the single-electrode voltage-clamp technique and a clear persistent, tetrodotoxin-sensitive component was isolated. This component was inhibited by 50% in a reversible way by 20 microM dopamine. These results show that dopamine increases the threshold for spike firing and suggest a mechanism for the inhibitory action of this neurotransmitter in the prefrontal cortex.